Academic Output in Global Surgery after the Lancet Commission on Global Surgery: A Scoping Review.

BACKGROUND: The Lancet Commission on Global Surgery (LCoGS) published its seminal report in 2015, carving a niche for global surgery academia. Six years after the LCoGS, a scoping review was conducted to see how the term 'global surgery' is characterized by the literature and how it relates to LCoGS and its domains. METHODS: PubMed was searched for publications between January 2015 and February 2021 that used the term 'global surgery' in the title, abstract, or key words or cited the LCoGS. Variables extracted included LCoGS domains, authorship metrics, geographic scope, and clinical specialty. RESULTS: The search captured 938 articles that qualified for data extraction. Nearly 80% of first and last authors had high-income country affiliations. Africa was the most frequently investigated region, though many countries within the region were under-represented. The World Journal of Surgery was the most frequent journal, publishing 13.9% of all articles. General surgery, pediatric surgery, and neurosurgery were the most represented specialties. Of the LCoGS domains, healthcare delivery and management were the most studied, while economics and financing were the least studied. CONCLUSION: A lack of consensus on the definition of global surgery remains. Additional research is needed in economics and financing, while obstetrics and trauma are under-represented in literature using the term 'global surgery'. Efforts in academic global surgery must give a voice to those carrying the global surgery agenda forward on the frontlines. Focusing on research capacity-building and encouraging contribution by local partners will lead to a stronger, more cohesive global surgery community.

Access to Essential Surgical Care in Chiapas, Mexico: A System-Wide Geospatial Analysis.

BACKGROUND: Long travel times to reach essential surgical care in Chiapas, Mexico's poorest state, can delay lifesaving procedures and contribute to adverse outcomes. Geographical access to surgical facilities is 1 of the 6 indicators of the Lancet Commission on Global Surgery and has been measured extensively worldwide. Our objective is to determine the population with 2-h geographical access to facilities capable of performing the Bellwether procedures (laparotomy, cesarean delivery, and open fracture repair). This is the first study in Mexico to assess access to surgical facilities, including both the fragmented public sector and the private sector. METHODS: In this cross-sectional study, conducted from June 2019 to January 2020, Bellwether capable surgical facilities from all health systems in Chiapas were geocoded and assessed through on-site data collection, Ministry of Health databases, and verified via telephone. Geospatial analyses were performed on Redivis. RESULTS: We identified 59 Bellwether capable hospitals, with 17.5% (n = 954,460) of the state residing more than 2 h from surgical care in public and private health systems. Of those, 22 facilities had confirmed 24/7 Bellwether capability, and 23% (n = 1,178,383) of the affiliated population resided more than 2 h from these hospitals. CONCLUSIONS: Our study shows that the Ministry of Health and employment-based health coverage could provide timely access to essential surgical care for the majority of the population. However, the fragmentation of the healthcare system leaves a gap that contributes to delays in care and unmet emergency surgical needs.

Innovation in early medical education, no bells or whistles required.

BACKGROUND: Despite a paucity of evidence to support a multitude of educational innovations, curricular leaders are pressured to find innovative solutions to better prepare medical students for an evolving twenty-first century health care system. As part of this effort, this study directly compared student-rated effectiveness scores of six different learning modalities. METHODS: Study participants included 286 medical students enrolled in the second-year rheumatology core at a single academic medical center between 2013 and 2017. Students were surveyed at the end of the core with a 15-item questionnaire, and student perceived effectiveness of six different learning modalities were compared. RESULTS: The modality that outperformed all others was Live Patient Encounters (LPE), with significantly higher student-rated effectiveness scores when compared to the referent modality of Problem-Based Learning (PBL). Using a 5-point Likert scale with responses ranging from "not effective" to "highly effective," LPE received a mean effectiveness score of 4.77 followed by Augenblick (4.21), PBL (4.11), Gout Racer video game (3.49), Rheumatology Remedy e-module (3.49), and simulation knee injection (3.09). CONCLUSIONS: Technologically advanced novel learning strategies were outperformed in this study by the more traditional active learning modality of LPE. This finding highlights the importance of testing innovative learning strategies at the level of the learner. Three additional conclusions can be drawn from this result. First, conflation of technology with innovation may lead to a myopic view of educational reform. Second, human factors seem to be responsible for the success of LPE and may have far-reaching educational rewards. Third, further applications of LPE should be tested in non-rheumatologic curricula. The relevance of this study is innately tied to the humanities-based application. While a formal qualitative analysis was not performed in this study, preliminary results suggest that live, structured patient interactions in the pre-clinical years of medical education may not only promote the learning of important educational objectives but also foster professional development, empathy, reflection, leadership, agency, and interpersonal skills. This "win-win" scenario (if true) would stand out as a rarity among strategic educational initiatives.

The prognostic effect of mechanical, ultrastructural, and ECM signatures in glioblastoma core and rim.

Glioblastoma (GBM) is a highly invasive, aggressive brain cancer that carries a median survival of 15 months and is resistant to standard therapeutics. Recent studies have demonstrated that intratumoral heterogeneity plays a critical role in promoting resistance by mediating tumor adaptation through microenvironmental cues. GBM can be separated into two distinct regions-a core and a rim, which are thought to drive specific aspects of tumor evolution. These differences in tumor progression are regulated by the diverse biomolecular and biophysical signals in these regions, but the acellular biophysical characteristics remain poorly described. This study investigates the mechanical and ultrastructural characteristics of the tumor extracellular matrix (ECM) in patient-matched GBM core and rim tissues. Seven patient-matched tumor core and rim samples and one non-neoplastic control were analyzed using atomic force microscopy, scanning electron microscopy, and immunofluorescence imaging to quantify mechanical, ultrastructural, and ECM composition changes. The results reveal significant differences in biophysical parameters between GBM core, rim, and non-neoplastic tissues. The GBM core is stiffer, denser, and is rich in ECM proteins hyaluronic acid and tenascin-C when compared to tumor rim and non-neoplastic tissues. These alterations are intimately related and have prognostic effect with stiff, dense tissue correlating with longer progression-free survival. These findings reveal new insights into the spatial heterogeneity of biophysical parameters in the GBM tumor microenvironment and identify a set of characteristics that may correlate with patient prognosis. In the long term, these characteristics may aid in the development of strategies to combat therapeutic resistance.

The current status of surgical care in the Asia-Pacific region and opportunities for improvement: proceedings.

The World Health Assembly resolution 68.15 recognised emergency and essential surgery as a critical component of universal health coverage. The first session of the three-part virtual meeting series on Strategic Planning to Improve Surgical, Obstetric, Anaesthesia, and Trauma Care in the Asia-Pacific Region focused on the current status of surgical care and opportunities for improvement. During this session, Ministries of Health and World Health Organization (WHO) Regional Directors shared country- and regional-level progress in surgical system strengthening. The WHO Western Pacific Regional Office (WPRO) has developed an Action Framework for Safe and Affordable Surgery, whilst the WHO South-East Asia Regional Office (SEARO) highlighted their efforts in emergency obstetric care, workforce strengthening, and blood safety. Numerous countries have begun developing and implementing National Surgical, Obstetric, and Anaesthesia Plans (NSOAPs). Participants agreed surgical system strengthening is an integral component of universal health coverage, pandemic preparedness, and overall health system resilience. Participants discussed common challenges, such as the COVID-19 pandemic, climate change, workforce capacity building, and improving access for hard-to-reach populations. They generated and shared common solutions, including strengthening surgical care capacity in first-level hospitals, anaesthesia task-shifting, remote training, and integrating surgical care with public health, preventive care, and emergency preparedness. Moving forward, participants committed to developing and implementing NSOAPs and agreed on the need to raise political awareness, build a broad-based movement, and form intersectoral collaborations.

Financing surgical, obstetric, anaesthesia, and trauma care in the Asia-Pacific region: proceedings.

Surgical, obstetric, and anaesthesia care saves lives, prevents disability, promotes economic prosperity, and is a fundamental human right. Session two of the three-part virtual meeting series on Strategic Planning to Improve Surgical, Obstetric, Anaesthesia, and Trauma Care in the Asia-Pacific Region discussed financing strategies for surgical care. During this session, participants made a robust case for investing in surgical care given its cost-effectiveness, macroeconomic benefits, and contribution to health security and pandemic preparedness. Funding for surgical system strengthening could arise from both domestic and international sources. Numerous strategies are available for mobilising funding for surgical care, including conducive macroeconomic growth, reprioritisation of health within government budgets, sector-specific domestic revenue, international financing, improving the effectiveness and efficiency of health budgets, and innovative financing. A wide range of funders recognised the importance of investing in surgical care and shared their currently funded projects in surgical, obstetric, anaesthesia, and trauma care as well as their funding priorities. Advocacy efforts to mobilise funding for surgical care to align with the existing funder priorities, such as primary health care, maternal and child health, health security, and the COVID-19 pandemic. Although the COVID-19 pandemic has constricted the fiscal space for surgical care, it has also brought unprecedented attention to health. Short-term investment in critical care, medical oxygen, and infection prevention and control as a part of the COVID-19 response must be leveraged to generate sustained strengthening of surgical systems beyond the pandemic.

Strategic planning to improve surgical, obstetric, anaesthesia, and trauma care in the Asia-Pacific region: introduction.

Surgical, obstetric, and anaesthesia care are required to treat one-third of the global disease burden. They have been recognised as an integral component of universal health coverage. However, five billion people lack access to safe and affordable surgical care when required. Countries in the Asia-Pacific region are currently developing strategies to strengthen their surgical care systems. The Strategic Planning to Improve Surgical, Obstetric, Anaesthesia, and Trauma Care in the Asia-Pacific Region meeting is a three-part virtual meeting series that brought together Ministries of Health, intergovernmental organisers, funders, professional associations, academic institutions, and nongovernmental organisations in the Asia-Pacific region. The meeting series took place over three virtual sessions in February and March 2021. Each session featured framing talks, panel presentations, and open discussions. Participants shared lessons about the challenges and solutions in surgical system strengthening, discussed funding opportunities, and forged strategic partnerships. Participants discussed strategies to build ongoing political momentum and mobilise funding, the implications of the COVID-19 pandemic and climate change on surgical care, the need to build a broad-based, inclusive movement, and leveraging remote technologies for workforce development and service delivery. This virtual meeting series is only the beginning of an ongoing community for knowledge sharing and strategic collaboration towards surgical system strengthening in the Asia-Pacific region.

Strategic partnerships to improve surgical care in the Asia-Pacific region: proceedings.

Emergency and essential surgery is a critical component of universal health coverage. Session three of the three-part virtual meeting series on Strategic Planning to Improve Surgical, Obstetric, Anaesthesia, and Trauma Care in the Asia-Pacific Region focused on strategic partnerships. During this session, a range of partner organisations, including intergovernmental organisations, professional associations, academic and research institutions, non-governmental organisations, and the private sector provided an update on their work in surgical system strengthening in the Asia-Pacific region. Partner organisations could provide technical and implementation support for National Surgical, Obstetric, and Anaesthesia Planning (NSOAP) in a number of areas, including workforce strengthening, capacity building, guideline development, monitoring and evaluation, and service delivery. Participants emphasised the importance of several forms of strategic collaboration: 1) collaboration across the spectrum of care between emergency, critical, and surgical care, which share many common underlying health system requirements; 2) interprofessional collaboration between surgery, obstetrics, anaesthesia, diagnostics, nursing, midwifery among other professions; 3) regional collaboration, particularly between Pacific Island Countries, and 4) South-South collaboration between low- and middle-income countries (LMICs) in mutual knowledge sharing. Partnerships between high-income countries (HIC) and LMIC organisations must include LMIC participants at a governance level for shared decision-making. Areas for joint action that emerged in the discussion included coordinated advocacy efforts to generate political view, developing common monitoring and evaluation frameworks, and utilising remote technology for workforce development and service delivery.

Rethinking referral systems in rural chiapas: A mixed methods study.

Background: Despite the assurance of universal health coverage, large disparities exist in access to surgery in the state of Chiapas. The purpose of this study was to determine the effectiveness of the surgical referral system at hospitals operated by the Ministry of Health in Chiapas. Methods: 13 variables were extracted from surgical referrals data from three public hospitals in Chiapas over a three-year period. Interviews were performed of health care workers involved in the referral system and surgical patients. The quantitative and qualitative data was analyzed convergently and reported using a narrative approach. Findings: In total, only 47.4% of referred patients requiring surgery received an operation. Requiring an elective, gynecological, or orthopedic surgery and each additional surgery cancellation were significantly associated with lower rates of receiving surgery. The impact of gender and surgical specialty, economic fragility of farmers, dependence upon economic resources to access care, pain leading people to seek care, and futility leading patients to abandon the public system were identified as main themes from the mixed methods analysis. Interpretation: Surgical referral patients in Chiapas struggle to navigate an inefficient and expensive system, leading to delayed care and forcing many patients to turn to the private health system. These mixed methods findings provide a detailed view of often overlooked limitations to universal health coverage in Chiapas. Moving forward, this knowledge must be applied to improve referral system coordination and provide hospitals with the necessary workforce, equipment, and protocols to ensure access to guaranteed care. Funding: Harvard University and the Abundance Fund provided funding for this project. Funding sources had no role in the writing of the manuscript or decision to submit it for publication.

Access and Financial Burden for Patients Seeking Essential Surgical Care in Pakistan.

Background: Pakistan is a lower middle-income country in South Asia with a population of over 220 million. With the recent development of national health programs focusing on surgical care, two areas of high priority for research and policy are access and financial risk protection related to surgery. This is the first study in Pakistan to nationally assess geographic access and expenditures for patients undergoing surgery. Methods: This is a cross-sectional study of patients undergoing laparotomy, cesarean section, and surgical management of a fracture at public tertiary care hospitals across the country. A validated financial risk protection tool was adapted for our study to collect data on the socio-economic characteristics of patients, geographic access, and out-of-pocket expenditure. Results: A total of 526 patients were surveyed at 13 public hospitals. 73.8% of patients had 2-hour access to the facility where they underwent their respective surgical procedures. A majority (53%) of patients were poor at baseline, and 79.5% and 70.3% of patients experienced catastrophic health expenditure and impoverishing health expenditure, respectively. Discussion: A substantial number of patients face long travel times to access essential surgical care and face a high percentage of impoverishing health expenditure and catastrophic health expenditure during this process. This study provides valuable baseline data to health policymakers for reform efforts that are underway. Conclusions: Strengthening surgical infrastructure and services in the existing network of public sector first-level facilities has the potential to dramatically improve emergency and essential surgical care across the country.

Interpersonal challenges in surgical care provision in rural Mexico: A qualitative study.

Background: Chiapas is among the states with the lowest access to health care in Mexico. A better understanding of the role of interpersonal relationships in referral systems could improve access to care in the region. The purpose of this study was to analyze the underlying barriers and facilitators to accessing surgical care at public hospitals run by the Ministry of Health in Chiapas. Methods: In this qualitative interview study, we performed semi-structured interviews with 19 surgical patients and 18 healthcare workers at three public hospitals in the Fraylesca Region of Chiapas to explore barriers and facilitators to successfully accessing surgical treatment. Transcripts were coded and analyzed using an inductive, thematic approach to data analysis. Findings: The five major themes identified as barriers to surgical care were dehumanization of patients, the toll of rehumanizing patients, animosity in the system, the refraction of violence onto patients, and poor resource coordination. Three themes identified as facilitators to receiving care were teamwork, social capital, and accompaniment. Interpretation: Health care workers described a culture of demoralization and mistrust within the health system worsened by a scarcity of resources. As a result, patient care is hampered by conflict, miscommunication, and feelings of dehumanization. Efforts to improve access to surgical care in the region should consider strategies to improve teamwork and expand patient accompaniment. Funding: Harvard University and the Abundance Fund provided funding for this project. Funding sources had no role in the writing of the manuscript or decision to submit it for publication.Resumen. Antecedentes: Chiapas es uno de los estados en Mexico con el menor acceso a la atención médica, y a los servicios quirúrgicos. Una mejor comprensión del papel de las relaciones interpersonales en los sistemas de referencias podría mejorar el acceso a la atención medica en la región. El objetivo del estudio es analizar las barreras y facilitadores para acceder a la atención quirúrgica en los hospitales públicos pertenecientes a la Secretaria de Salud del estado de Chiapas. Método: En este estudio cualitativo, realizamos entrevistas semiestructuradas con 19 pacientes quirúrgicos y 18 trabajadores de la salud en tres hospitales públicos en la región de la Frailesca de Chiapas para explorar barreras y facilitadores para acceder al tratamiento quirúrgico. Las transcripciones se codificaron y analizaron utilizando un enfoque temático. Resultados: Las cinco barreras principales identificadas fueron la deshumanización de los pacientes, el costo a re humanizar pacientes, la animosidad en el sistema, la refracción de la violencia sobre los pacientes y la mala coordinación de recursos. Tres facilitadores para recibir cirugía fueron el trabajo en equipo, el capital social, y el acompañamiento. Interpretaciones: Los trabajadores de la salud describieron una cultura de desmoralización y desconfianza en el sistema de salud que se agrava con la escasez de recursos. Como resultado se obtiene, conflicto, falta de comunicación, y sentimientos de deshumanización que empeoran la atención al paciente. Recomendaciones para mejorar el acceso a los servicios quirúrgicos en la región incluyen estrategias para mejorar el trabajo en equipo y ampliar el acompañamiento de los pacientes. Financiamiento: La Universidad de Harvard y the Abundance Fund proporcionaron fondos para este proyecto. Las fuentes de financiamiento no influyen en la redacción ni en la publicación del manuscrito.

What do patients with glaucoma see: a novel iPad app to improve glaucoma patient awareness of visual field loss.

PURPOSE: Glaucoma patients with peripheral vision loss have in the past subjectively described their field loss as 'blurred' or 'no vision compromise'. We developed an iPad app for patients to self-characterise perception within areas of glaucomatous visual field loss. METHODS: Twelve glaucoma patients with visual acuity ≥20/40 in each eye, stable and reliable Humphrey Visual Field (HVF) over 2 years were enrolled. An iPad app (held at 33 cm) allowed subjects to modify 'blur' or 'dimness' to match their perception of a 2×2 m wall-mounted poster at 1 m distance. Subjects fixated at the centre of the poster (spanning 45° of field from centre). The output was degree of blur/dim: normal, mild and severe noted on the iPad image at the 54 retinal loci tested by the HVF 24-2 and was compared to threshold sensitivity values at these loci. Monocular (Right eye (OD), left eye (OS)) HVF responses were used to calculate an integrated binocular (OU) visual field index (VFI). All three data sets were analysed separately. RESULTS: 36 HVF and iPad responses from 12 subjects (mean age 71±8.2y) were analysed. The mean VFI was 77% OD, 76% OS, 83% OU. The most common iPad response reported was normal followed by blur. No subject reported dim response. The mean HVF sensitivity threshold was significantly associated with the iPad response at the corresponding retinal loci (For OD, OS and OU, respectively (dB): normal: 23, 25, 27; mild blur: 18, 16, 22; severe blur: 9, 9, 11). On receiver operative characteristic (ROC) curve analysis, the HVF retinal sensitivity cut-off at which subjects reported blur was 23.4 OD, 23 OS and 23.3 OU (dB). CONCLUSIONS: Glaucoma subjects self-pictorialised their field defects as blur; never dim or black. Our innovation allows translation of HVF data to quantitatively characterise visual perception in patients with glaucomatous field defects.

Melanization of flavonoids by fungal and bacterial laccases.

Laccase activity in plants results in the formation of a number of brown pigments, often referred to as tannins. Laccase-dependent pigment production is also catalogued in numerous fungal and bacterial species. The laccase of the haploid yeast Cryptococcus neoformans forms melanin-like pigmentation outside the cell wall in the presence of exogenous substrates. While this process is a contributing factor to its virulence in humans, the evolutionary intent for the laccase function remains a mystery. We show here that C. neoformans and Bacillus subtilis have the ability to create melanin-like pigments from a variety of flavonoid molecules across a range of conformations, preferring those with 3',4'-dihydroxylations. Since flavonoids are ubiquitous plant molecules and often-considered antimicrobial agents, we postulate that they are the intended natural targets of laccase activity and result in the formation of a defensive melanin-like coat. These results suggests a new mechanism by which flavonoid-melanin formation may occur, using not only A- and C-ring linkages, but also monomer links through the B-ring of the flavonoid structure. We also show that resveratrol and other non- and mono-hydroxylated polyphenol substrates have the ability to restrict pigment formation and may be potent inhibitors of laccase activity.

Genome-scale metabolic network modeling results in minimal interventions that cooperatively force carbon flux towards malonyl-CoA.

Malonyl-coenzyme A is an important precursor metabolite for the biosynthesis of polyketides, flavonoids and biofuels. However, malonyl-CoA naturally synthesized in microorganisms is consumed for the production of fatty acids and phospholipids leaving only a small amount available for the production of other metabolic targets in recombinant biosynthesis. Here we present an integrated computational and experimental approach aimed at improving the intracellular availability of malonyl-CoA in Escherichia coli. We used a customized version of the recently developed OptForce methodology to predict a minimal set of genetic interventions that guarantee a prespecified yield of malonyl-CoA in E. coli strain BL21 Star™. In order to validate the model predictions, we have successfully constructed an E. coli recombinant strain that exhibits a 4-fold increase in the levels of intracellular malonyl-CoA compared to the wild type strain. Furthermore, we demonstrate the potential of this E. coli strain for the production of plant-specific secondary metabolites naringenin (474mg/L) with the highest yield ever achieved in a lab-scale fermentation process. Combined effect of the genetic interventions was found to be synergistic based on a developed analysis method that correlates genetic modification to cell phenotype, specifically the identified knockout targets (ΔfumC and ΔsucC) and overexpression targets (ACC, PGK, GAPD and PDH) can cooperatively force carbon flux towards malonyl-CoA. The presented strategy can also be readily expanded for the production of other malonyl-CoA-derived compounds like polyketides and biofuels.

High-yield resveratrol production in engineered Escherichia coli.

Plant polyphenols have been the subject of several recent scientific investigations since many of the molecules in this class have been found to be highly active in the human body, with a plethora of health-promoting activities against a variety of diseases, including heart disease, diabetes, and cancer, and with even the potential to slow aging. Further development of these potent natural therapeutics hinges on the formation of robust industrial production platforms designed using specifically selected as well as engineered protein sources along with the construction of optimal expression platforms. In this work, we first report the investigation of various stilbene synthases from an array of plant species considering structure-activity relationships, their expression efficiency in microorganisms, and their ability to synthesize resveratrol. Second, we looked into the construct environment of recombinantly expressed stilbene synthases, including different promoters, construct designs, and host strains, to create an Escherichia coli strain capable of producing superior resveratrol titers sufficient for commercial usage. Further improvement of metabolic capabilities of the recombinant strain aimed at improving the intracellular malonyl-coenzyme A pool, a resveratrol precursor, resulted in a final improved titer of 2.3 g/liter resveratrol.

Assessment of surgical capacity in Chiapas, Mexico: a cross-sectional study of the public and private sector.

INTRODUCTION: Surgical, anaesthesia and obstetric (SAO) care are essential, life-saving components of universal healthcare. In Chiapas, Mexico's southernmost state, the capacity of SAO care is unknown. This study aims to assess the surgical capacity in Chiapas, Mexico, as it relates to access, infrastructure, service delivery, surgical volume, quality, workforce and financial risk protection. METHODS: A cross-sectional study of Ministry of Health public hospitals and private hospitals in Chiapas was performed. The translated Surgical Assessment Tool (SAT) was implemented in sampled hospitals. Surgical volume was collected retrospectively from hospital logbooks. Fisher's exact test and Mann-Whitney U test were used to compare public and private hospitals. Catastrophic expenditure from surgical care was calculated. RESULTS: Data were collected from 17 public hospitals and 20 private hospitals in Chiapas. Private hospitals were smaller than public hospitals and public hospitals performed more surgeries per operating room. Not all hospitals reported consistent electricity, running water or oxygen, but private hospitals were more likely to have these basic infrastructure components compared with public hospitals (84% vs 95%; 60% vs 100%; 94.1% vs 100%, respectively). Bellwether surgical procedures performed in private hospitals cost significantly more, and posed a higher risk of catastrophic expenditure, than those performed in public hospitals. CONCLUSION: Capacity limitations are greater in public hospitals compared with private hospitals. However, the cost of care in the private sector is significantly higher than the public sector and may result in catastrophic expenditures. Targeted interventions to improve the infrastructure, workforce availability and data collection are needed.

Improving NADPH availability for natural product biosynthesis in Escherichia coli by metabolic engineering.

With microbial production becoming the primary choice for natural product synthesis, increasing precursor and cofactor availability has become a chief hurdle for the generation of efficient production platforms. As such, we employed a stoichiometric-based model to identify combinations of gene knockouts for improving NADPH availability in Escherichia coli. Specifically, two different model objectives were used to identify possible genotypes that exhibited either improved overall NADPH production or an improved flux through an artificial reaction coupling NADPH yield to biomass. The top single, double and triple gene deletion candidates were constructed and as a case study evaluated for their ability to produce two polyphenols, leucocyanidin and (+)-catechin. Each is derived from their common precursor dihydroquercetin using two recombinant NADPH-dependent enzymes: dihydroflavonol 4-reductase and leucoanthocyanidin reductase. The best engineered strain carrying Delta pgi, Delta ppc and Delta pldA deletions accumulated up to 817 mg/L of leucocyanidin and 39 mg/L (+)-catechin in batch culture with 10 g/L glucose in modified M9 medium, a 4-fold and 2-fold increase, respectively, compared to the wild-type control.

Projected impact of COVID-19 mitigation strategies on hospital services in the Mexico City Metropolitan Area.

Evidence-based models may assist Mexican government officials and health authorities in determining the safest plans to respond to the coronavirus disease 2019 (COVID-19) pandemic in the most-affected region of the country, the Mexico City Metropolitan Area. This study aims to present the potential impacts of COVID-19 in this region and to model possible benefits of mitigation efforts. The COVID-19 Hospital Impact Model for Epidemics was used to estimate the probable evolution of COVID-19 in three scenarios: (i) no social distancing, (ii) social distancing in place at 50% effectiveness, and (iii) social distancing in place at 60% effectiveness. Projections of the number of inpatient hospitalizations, intensive care unit admissions, and patients requiring ventilators were made for each scenario. Using the model described, it was predicted that peak case volume at 0% mitigation was to occur on April 30, 2020 at 11,553,566 infected individuals. Peak case volume at 50% mitigation was predicted to occur on June 1, 2020 with 5,970,093 infected individuals and on June 21, 2020 for 60% mitigation with 4,128,574 infected individuals. Occupancy rates in hospitals during peak periods at 0%, 50%, and 60% mitigation would be 875.9%, 322.8%, and 203.5%, respectively, when all inpatient beds are included. Under these scenarios, peak daily hospital admissions would be 40,438, 13,820, and 8,650. Additionally, 60% mitigation would result in a decrease in peak intensive care beds from 94,706 to 23,116 beds and a decrease in peak ventilator need from 67,889 to 17,087 units. Mitigating the spread of COVID-19 through social distancing could have a dramatic impact on reducing the number of infected people and minimize hospital overcrowding. These evidence-based models may enable careful resource utilization and encourage targeted public health responses.

Assessment of diagnostics capacity in hospitals providing surgical care in two Latin American states.

BACKGROUND: Diagnostic services are an essential component of high-quality surgical, anesthesia and obstetric (SAO) care. Efforts to scale up SAO care in Latin America have often overlooked diagnostics capacity. This study aims to analyze the capacity of diagnostic services, including radiology, pathology, and laboratory medicine, in hospitals providing SAO care in the states of Chiapas, Mexico and Amazonas, Brazil. METHODS: A stratified cross-sectional evaluation of diagnostic capacity in hospitals performing surgery in Chiapas and Amazonas was performed using the Surgical Assessment Tool (SAT). National data sources were queried for indicators of diagnostics capacity in terms of workforce, infrastructure and diagnosis utilization. Fisher's exact tests and chi-square tests were used to compare categorical variables between the private and public sector in Chiapas while descriptive statistics are used to compare Amazonas and Chiapas. FINDINGS: In Chiapas, 53% (n = 17) of public and 34% (n = 20) of private hospitals providing SAO care were assessed. More private hospitals than public hospitals could always provide x-rays (35% vs 23.5%) and ultrasound (85% vs 47.1%). However neither sector could consistently perform basic laboratory testing such as complete blood counts (70.6% public, 65% private). In Amazonas, 30% (n = 18) of rural hospitals were surveyed. Most had functioning x-ray machine (77.8%) and ultrasound (55.6%). The majority of hospitals could provide complete blood count (66.7%) but only one hospital (5.6%) could always perform an infectious panel. Both Chiapas and Amazonas had dramatically fewer diagnostic practitioners per capita in each state compared to the national average capacity. INTERPRETATION: Facilities providing SAO care in low-resource states in Mexico and Brazil often lack functioning diagnostics services and workforce. Scale-up of diagnostic services is essential to improve SAO care and should occur with emphasis on equitable and adequate resource allocation.

Increased malonyl coenzyme A biosynthesis by tuning the Escherichia coli metabolic network and its application to flavanone production.

Identification of genetic targets able to bring about changes to the metabolite profiles of microorganisms continues to be a challenging task. We have independently developed a cipher of evolutionary design (CiED) to identify genetic perturbations, such as gene deletions and other network modifications, that result in optimal phenotypes for the production of end products, such as recombinant natural products. Coupled to an evolutionary search, our method demonstrates the utility of a purely stoichiometric network to predict improved Escherichia coli genotypes that more effectively channel carbon flux toward malonyl coenzyme A (CoA) and other cofactors in an effort to generate recombinant strains with enhanced flavonoid production capacity. The engineered E. coli strains were constructed first by the targeted deletion of native genes predicted by CiED and then second by incorporating selected overexpressions, including those of genes required for the coexpression of the plant-derived flavanones, acetate assimilation, acetyl-CoA carboxylase, and the biosynthesis of coenzyme A. As a result, the specific flavanone production from our optimally engineered strains was increased by over 660% for naringenin (15 to 100 mg/liter/optical density unit [OD]) and by over 420% for eriodictyol (13 to 55 mg/liter/OD).